Jumbo Phages: A Comparative Genomic Overview of Core Functions and Adaptions for Biological Conflicts

Jumbo phages have attracted much attention by virtue of their extraordinary genome size and unusual aspects of biology. By performing a comparative genomics analysis of 224 jumbo phages, we suggest an objective inclusion criterion based on genome size distributions and present a synthetic overview of their manifold adaptations across major biological systems. By means of clustering and principal component analysis of the phyletic patterns of conserved genes, all known jumbo phages can be classified into three higher-order groups, which include both myoviral and siphoviral morphologies indicating multiple independent origins from smaller predecessors. Our study uncovers several under-appreciated or unreported aspects of the DNA replication, recombination, transcription and virion maturation systems. Leveraging sensitive sequence analysis methods, we identify novel protein-modifying enzymes that might help hijack the host-machinery. Focusing on host–virus conflicts, we detect strategies used to counter different wings of the bacterial immune system, such as cyclic nucleotide- and NAD+-dependent effector-activation, and prevention of superinfection during pseudolysogeny. We reconstruct the RNA-repair systems of jumbo phages that counter the consequences of RNA-targeting host effectors. These findings also suggest that several jumbo phage proteins provide a snapshot of the systems found in ancient replicons preceding the last universal ancestor of cellular life.

[1]  C. Duffy,et al.  Jumbo Phages , 2021, Encyclopedia of Virology.

[2]  J. Claverie,et al.  Investigating the Concept and Origin of Viruses , 2020, Trends in Microbiology.

[3]  M. Sokolova,et al.  Multisubunit RNA Polymerases of Jumbo Bacteriophages , 2020, Viruses.

[4]  Q. She,et al.  A Membrane-Associated DHH-DHHA1 Nuclease Degrades Type III CRISPR Second Messenger. , 2020, Cell reports.

[5]  Wieland Steinchen,et al.  (p)ppGpp: Magic Modulators of Bacterial Physiology and Metabolism , 2020, Frontiers in Microbiology.

[6]  M. Voet,et al.  The Phage-Encoded N-Acetyltransferase Rac Mediates Inactivation of Pseudomonas aeruginosa Transcription by Cleavage of the RNA Polymerase Alpha Subunit , 2020, Viruses.

[7]  L. Aravind,et al.  Identification of Uncharacterized Components of Prokaryotic Immune Systems and Their Diverse Eukaryotic Reformulations , 2020, Journal of Bacteriology.

[8]  J. Bondy-Denomy,et al.  Intracellular Organization by Jumbo Bacteriophages , 2020, Journal of bacteriology.

[9]  S. Wolin,et al.  The Bacterial Ro60 Protein and Its Noncoding Y RNA Regulators. , 2020, Annual review of microbiology.

[10]  D. Kihara,et al.  Phage G Structure at 6.1 Å Resolution, Condensed DNA, and Host Identity Revision to a Lysinibacillus. , 2020, Journal of molecular biology.

[11]  L. Aravind,et al.  Highly regulated, diversifying NTP-dependent biological conflict systems with implications for the emergence of multicellularity , 2020, eLife.

[12]  M. Borgnia,et al.  Structures of AAA protein translocase Bcs1 suggest translocation mechanism of a folded protein , 2020, Nature Structural & Molecular Biology.

[13]  F. Rohwer,et al.  Gp4 is a nuclease required for morphogenesis of T4-like bacteriophages. , 2020, Virology.

[14]  Beiyan Nan,et al.  Second messengers and divergent HD‐GYP phosphodiesterases regulate 3′,3′‐cGAMP signaling , 2020, Molecular microbiology.

[15]  V. Arcus,et al.  PhoH2 proteins couple RNA helicase and RNAse activities , 2019, Protein science : a publication of the Protein Society.

[16]  Peter C. Fineran,et al.  A jumbo phage that forms a nucleus-like structure evades CRISPR–Cas DNA targeting but is vulnerable to type III RNA-based immunity , 2019, Nature Microbiology.

[17]  T. Nakai,et al.  A novel jumbo Tenacibaculum maritimum lytic phage with head-fiber-like appendages , 2019, Archives of Virology.

[18]  M. Tarry,et al.  Structures of GapR reveal a central channel which could accommodate B-DNA , 2019, Scientific Reports.

[19]  Y. Goldgur,et al.  Atomic structures of the RNA end-healing 5′-OH kinase and 2′,3′-cyclic phosphodiesterase domains of fungal tRNA ligase: conformational switches in the kinase upon binding of the GTP phosphate donor , 2019, Nucleic acids research.

[20]  D. Agard,et al.  A bacteriophage nucleus-like compartment shields DNA from CRISPR nucleases , 2019, Nature.

[21]  Eui-Hwan Chung,et al.  TIR domains of plant immune receptors are NAD+-cleaving enzymes that promote cell death , 2019, Science.

[22]  K. Haubrich,et al.  Emerging RNA-binding roles in the TRIM family of ubiquitin ligases , 2019, Biological chemistry.

[23]  L. Aravind,et al.  Oxidative opening of the aromatic ring: Tracing the natural history of a large superfamily of dioxygenase domains and their relatives , 2019, The Journal of Biological Chemistry.

[24]  L. Aravind,et al.  The Origin and Evolution of Release Factors: Implications for Translation Termination, Ribosome Rescue, and Quality Control Pathways , 2019, International journal of molecular sciences.

[25]  Christine L. Sun,et al.  Clades of huge phages from across Earth’s ecosystems , 2019, bioRxiv.

[26]  P. J. Kranzusch,et al.  Bacterial cGAS-like enzymes synthesize diverse nucleotide signals , 2019, Nature.

[27]  D. Svergun,et al.  An NAD+ Phosphorylase Toxin Triggers Mycobacterium tuberculosis Cell Death , 2019, Molecular cell.

[28]  L. Marraffini,et al.  (Ph)ighting Phages: How Bacteria Resist Their Parasites. , 2019, Cell host & microbe.

[29]  P. J. Kranzusch,et al.  Viral and metazoan poxins are cGAMP-specific nucleases that restrict cGAS-STING signaling , 2019, Nature.

[30]  H. Nishimasu,et al.  Cap-specific terminal N6-methylation of RNA by an RNA polymerase II–associated methyltransferase , 2019, Science.

[31]  B. Alberts,et al.  In vitro reconstitution of DNA replication initiated by genetic recombination: a T4 bacteriophage model for a type of DNA synthesis important for all cells , 2019, Molecular biology of the cell.

[32]  P. Knipscheer,et al.  The role of SLX4 and its associated nucleases in DNA interstrand crosslink repair , 2018, Nucleic acids research.

[33]  D. Brodersen,et al.  The RES domain toxins of RES‐Xre toxin‐antitoxin modules induce cell stasis by degrading NAD+ , 2018, Molecular microbiology.

[34]  E. Koonin,et al.  Evolution of the Large Nucleocytoplasmic DNA Viruses of Eukaryotes and Convergent Origins of Viral Gigantism. , 2019, Advances in virus research.

[35]  G. Salmond,et al.  Jumbo Bacteriophages Are Represented Within an Increasing Diversity of Environmental Viruses Infecting the Emerging Phytopathogen, Dickeya solani , 2018, Front. Microbiol..

[36]  P. Lavender,et al.  CRISPR‐based reagents to study the influence of the epigenome on gene expression , 2018, Clinical and experimental immunology.

[37]  K. Shi,et al.  T4 DNA ligase structure reveals a prototypical ATP-dependent ligase with a unique mode of sliding clamp interaction , 2018, Nucleic acids research.

[38]  Pamela J. B. Brown,et al.  Larger Than Life: Isolation and Genomic Characterization of a Jumbo Phage That Infects the Bacterial Plant Pathogen, Agrobacterium tumefaciens , 2018, Front. Microbiol..

[39]  N. Ruiz,et al.  Function and Biogenesis of Lipopolysaccharides , 2018, EcoSal Plus.

[40]  Brian C. Thomas,et al.  Megaphages infect Prevotella and variants are widespread in gut microbiomes , 2018, bioRxiv.

[41]  C. Waters,et al.  Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae , 2018, Proceedings of the National Academy of Sciences.

[42]  M. Loessner,et al.  Erwinia amylovora phage vB_EamM_Y3 represents another lineage of hairy Myoviridae. , 2018, Research in microbiology.

[43]  H. Ogata,et al.  Xanthomonas citri jumbo phage XacN1 exhibits a wide host range and high complement of tRNA genes , 2018, Scientific Reports.

[44]  J. Milbrandt,et al.  TIR Domain Proteins Are an Ancient Family of NAD+-Consuming Enzymes , 2018, Current Biology.

[45]  H. Kumar,et al.  Viral deubiquitinases: role in evasion of anti-viral innate immunity , 2017, Critical reviews in microbiology.

[46]  G. Brouhard,et al.  A microtubule bestiary: structural diversity in tubulin polymers , 2017, Molecular biology of the cell.

[47]  J. Conway,et al.  Capsids and Genomes of Jumbo-Sized Bacteriophages Reveal the Evolutionary Reach of the HK97 Fold , 2017, mBio.

[48]  Soon-jong Kim,et al.  Structural analyses of the MazEF4 toxin-antitoxin pair in Mycobacterium tuberculosis provide evidence for a unique extracellular death factor , 2017, The Journal of Biological Chemistry.

[49]  Frank Schwede,et al.  Type III CRISPR–Cas systems produce cyclic oligoadenylate second messengers , 2017, Nature.

[50]  L. Aravind,et al.  Polyvalent Proteins, a Pervasive Theme in the Intergenomic Biological Conflicts of Bacteriophages and Conjugative Elements , 2017, Journal of bacteriology.

[51]  M. Lieber,et al.  Non-homologous DNA end joining and alternative pathways to double-strand break repair , 2017, Nature Reviews Molecular Cell Biology.

[52]  J. Milbrandt,et al.  The SARM1 Toll/Interleukin-1 Receptor Domain Possesses Intrinsic NAD+ Cleavage Activity that Promotes Pathological Axonal Degeneration , 2017, Neuron.

[53]  E. S. Miller,et al.  Vibrio Phage KVP40 Encodes a Functional NAD+ Salvage Pathway , 2017, Journal of bacteriology.

[54]  H. Neve,et al.  Things Are Getting Hairy: Enterobacteria Bacteriophage vB_PcaM_CBB , 2017, Front. Microbiol..

[55]  S. Weintraub,et al.  Identification of Essential Genes in the Salmonella Phage SPN3US Reveals Novel Insights into Giant Phage Head Structure and Assembly , 2016, Journal of Virology.

[56]  M. Delarue,et al.  Shared active site architecture between archaeal PolD and multi-subunit RNA polymerases revealed by X-ray crystallography , 2016, Nature Communications.

[57]  L. Aravind,et al.  RNA damage in biological conflicts and the diversity of responding RNA repair systems , 2016, Nucleic acids research.

[58]  E. Koonin,et al.  The genome of AR9, a giant transducing Bacillus phage encoding two multisubunit RNA polymerases. , 2016, Virology.

[59]  E. Raleigh,et al.  Biosynthesis and Function of Modified Bases in Bacteria and Their Viruses. , 2016, Chemical reviews.

[60]  I. Ahel,et al.  Macrodomains: Structure, Function, Evolution, and Catalytic Activities. , 2016, Annual review of biochemistry.

[61]  C. Dienemann,et al.  Transcription initiation complex structures elucidate DNA opening , 2016, Nature.

[62]  A. Oakley Dynamics of Open DNA Sliding Clamps , 2016, PloS one.

[63]  M. Singer,et al.  A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus , 2016, PLoS genetics.

[64]  TuAnh N. Huynh,et al.  Too much of a good thing: regulated depletion of c-di-AMP in the bacterial cytoplasm. , 2016, Current opinion in microbiology.

[65]  J. Blanchard,et al.  Bacterial GCN5-Related N-Acetyltransferases: From Resistance to Regulation. , 2016, Biochemistry.

[66]  Robert D. Finn,et al.  The Pfam protein families database: towards a more sustainable future , 2015, Nucleic Acids Res..

[67]  L. Aravind,et al.  Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification , 2015, BioEssays : news and reviews in molecular, cellular and developmental biology.

[68]  L. Aravind,et al.  Comparative genomic analyses reveal a vast, novel network of nucleotide-centric systems in biological conflicts, immunity and signaling , 2015, Nucleic acids research.

[69]  M. Feiss,et al.  Mechanisms of DNA Packaging by Large Double-Stranded DNA Viruses. , 2015, Annual review of virology.

[70]  K. Makarova,et al.  A non-canonical multisubunit RNA polymerase encoded by a giant bacteriophage , 2015, Nucleic acids research.

[71]  G. Kaufmann,et al.  Phage T4‐induced DNA breaks activate a tRNA repair‐defying anticodon nuclease , 2015, Molecular microbiology.

[72]  M. Loessner,et al.  Putative type 1 thymidylate synthase and dihydrofolate reductase as signature genes of a novel bastille-like group of phages in the subfamily Spounavirinae , 2015, BMC Genomics.

[73]  J. Essigmann,et al.  The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond* , 2015, The Journal of Biological Chemistry.

[74]  Sriram Subramaniam,et al.  Cryo-EM structure of the bacteriophage T4 portal protein assembly at near-atomic resolution , 2015, Nature Communications.

[75]  V. Arcus,et al.  The mycobacterial PhoH2 proteins are type II toxin antitoxins coupled to RNA helicase domains. , 2015, Tuberculosis.

[76]  K. Seed Battling Phages: How Bacteria Defend against Viral Attack , 2015, PLoS pathogens.

[77]  L. Aravind,et al.  The eukaryotic translation initiation regulator CDC123 defines a divergent clade of ATP-grasp enzymes with a predicted role in novel protein modifications , 2015, Biology Direct.

[78]  L. Aravind,et al.  Proteasomal control of cytokinin synthesis protects Mycobacterium tuberculosis against nitric oxide. , 2015, Molecular cell.

[79]  L. Aravind,et al.  The natural history of ADP-ribosyltransferases and the ADP-ribosylation system. , 2015, Current topics in microbiology and immunology.

[80]  V. Hornung,et al.  OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids , 2014, Nature Reviews Immunology.

[81]  Julie Bianchi,et al.  PrimPol—A new polymerase on the block , 2014, Molecular & cellular oncology.

[82]  M. F. White,et al.  CARF and WYL domains: ligand-binding regulators of prokaryotic defense systems , 2014, Front. Genet..

[83]  Y. Sakaguchi,et al.  Intragenus generalized transduction in Staphylococcus spp. by a novel giant phage , 2014, The ISME Journal.

[84]  M. Rossmann,et al.  Molecular architecture of tailed double-stranded DNA phages , 2014, Bacteriophage.

[85]  S. Yamashita,et al.  Translocation and rotation of tRNA during template-independent RNA polymerization by tRNA nucleotidyltransferase. , 2014, Structure.

[86]  Ruben C. Arslan Evolutionary Genetics , 2014 .

[87]  E. W. Moomaw,et al.  Protein Similarity Networks Reveal Relationships among Sequence, Structure, and Function within the Cupin Superfamily , 2013, PloS one.

[88]  J. Mekalanos,et al.  PAAR-repeat proteins sharpen and diversify the Type VI secretion system spike , 2013, Nature.

[89]  Zhijian J. Chen,et al.  Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. , 2013, Molecules and Cells.

[90]  R. Silverman,et al.  Homologous 2′,5′-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity , 2013, Proceedings of the National Academy of Sciences.

[91]  L. Aravind,et al.  Computational identification of novel biochemical systems involved in oxidation, glycosylation and other complex modifications of bases in DNA , 2013, Nucleic acids research.

[92]  Christopher H. S. Aylett,et al.  Structure of the Tubulin/FtsZ-Like Protein TubZ from Pseudomonas Bacteriophage ΦKZ , 2013, Journal of molecular biology.

[93]  R. Meškys,et al.  Klebsiella Phage vB_KleM-RaK2 — A Giant Singleton Virus of the Family Myoviridae , 2013, PloS one.

[94]  E. Koonin,et al.  Live virus-free or die: coupling of antivirus immunity and programmed suicide or dormancy in prokaryotes , 2012, Biology Direct.

[95]  L. Aravind,et al.  Ter-dependent stress response systems: novel pathways related to metal sensing, production of a nucleoside-like metabolite, and DNA-processing. , 2012, Molecular bioSystems.

[96]  Christelle Breton,et al.  Recent structures, evolution and mechanisms of glycosyltransferases. , 2012, Current opinion in structural biology.

[97]  L. Aravind,et al.  Insights from the architecture of the bacterial transcription apparatus. , 2012, Journal of structural biology.

[98]  Edward C. Uberbacher,et al.  Gene and translation initiation site prediction in metagenomic sequences , 2012, Bioinform..

[99]  K. Raney,et al.  The T4 phage SF1B helicase Dda is structurally optimized to perform DNA strand separation. , 2012, Structure.

[100]  L. Aravind,et al.  Gene flow and biological conflict systems in the origin and evolution of eukaryotes , 2012, Front. Cell. Inf. Microbio..

[101]  Vivek Anantharaman,et al.  Polymorphic toxin systems: Comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomics , 2012, Biology Direct.

[102]  G. Kaufmann,et al.  The wobble nucleotide-excising anticodon nuclease RloC is governed by the zinc-hook and DNA-dependent ATPase of its Rad50-like region , 2012, Nucleic acids research.

[103]  L. Aravind,et al.  Identification of novel components of NAD-utilizing metabolic pathways and prediction of their biochemical functions. , 2012, Molecular bioSystems.

[104]  Y. Sakaguchi,et al.  Tubulin homolog TubZ in a phage-encoded partition system , 2012, Proceedings of the National Academy of Sciences.

[105]  Dennis C Winkler,et al.  Extensive proteolysis of head and inner body proteins by a morphogenetic protease in the giant Pseudomonas aeruginosa phage φKZ , 2012, Molecular microbiology.

[106]  G. Węgrzyn,et al.  Chapter 9 - Pseudolysogeny , 2012 .

[107]  L. Black,et al.  Structure, assembly, and DNA packaging of the bacteriophage T4 head. , 2012, Advances in virus research.

[108]  K. Truscott,et al.  The N-end rule pathway: from recognition by N-recognins, to destruction by AAA+proteases. , 2012, Biochimica et biophysica acta.

[109]  P. Satir,et al.  The ciliary cytoskeleton. , 2012, Comprehensive Physiology.

[110]  E. Geiduschek,et al.  Crystal structure of the bacteriophage T4 late-transcription coactivator gp33 with the β-subunit flap domain of Escherichia coli RNA polymerase , 2011, Proceedings of the National Academy of Sciences.

[111]  Graham F Hatfull,et al.  Bacteriophages and their genomes. , 2011, Current opinion in virology.

[112]  S. Casjens,et al.  Atomic Structure of Bacteriophage Sf6 Tail Needle Knob* , 2011, The Journal of Biological Chemistry.

[113]  K. Gerdes,et al.  Enteric virulence associated protein VapC inhibits translation by cleavage of initiator tRNA , 2011, Proceedings of the National Academy of Sciences.

[114]  R. Garrett,et al.  Chaperone Role for Proteins p618 and p892 in the Extracellular Tail Development of Acidianus Two-Tailed Virus , 2011, Journal of Virology.

[115]  M. Welch,et al.  The Pseudomonas aeruginosa generalized transducing phage phiPA3 is a new member of the phiKZ-like group of 'jumbo' phages, and infects model laboratory strains and clinical isolates from cystic fibrosis patients. , 2011, Microbiology.

[116]  S. Shuman,et al.  RtcB Is the RNA Ligase Component of an Escherichia coli RNA Repair Operon* , 2011, The Journal of Biological Chemistry.

[117]  L. Aravind,et al.  Natural history of eukaryotic DNA methylation systems. , 2011, Progress in molecular biology and translational science.

[118]  S. Shuman,et al.  RNA 3′-Phosphate Cyclase (RtcA) Catalyzes Ligase-like Adenylylation of DNA and RNA 5′-Monophosphate Ends* , 2010, The Journal of Biological Chemistry.

[119]  Katherine H. Huang,et al.  Genomic analysis of oceanic cyanobacterial myoviruses compared with T4-like myoviruses from diverse hosts and environments , 2010, Environmental microbiology.

[120]  M. Belfort,et al.  Mobile DNA elements in T4 and related phages , 2010, Virology Journal.

[121]  D. Hinton Transcriptional control in the prereplicative phase of T4 development , 2010, Virology Journal.

[122]  B. Stoddard,et al.  Social networking between mobile introns and their host genes , 2010, Molecular microbiology.

[123]  Yaning Qi,et al.  2',3'-cAMP hydrolysis by metal-dependent phosphodiesterases containing DHH, EAL, and HD domains is non-specific: Implications for PDE screening. , 2010, Biochemical and biophysical research communications.

[124]  K. Severinov,et al.  Determinants of affinity and activity of the anti-sigma factor AsiA. , 2010, Biochemistry.

[125]  R. Bourret Receiver domain structure and function in response regulator proteins. , 2010, Current opinion in microbiology.

[126]  Paramvir S. Dehal,et al.  FastTree 2 – Approximately Maximum-Likelihood Trees for Large Alignments , 2010, PloS one.

[127]  L. Aravind,et al.  Diversity and evolution of chromatin proteins encoded by DNA viruses. , 2010, Biochimica et biophysica acta.

[128]  Saraswathi Abhiman,et al.  Amidoligases with ATP-grasp, glutamine synthetase-like and acetyltransferase-like domains: synthesis of novel metabolites and peptide modifications of proteins. , 2009, Molecular bioSystems.

[129]  Dongwei Zhang,et al.  YybT Is a Signaling Protein That Contains a Cyclic Dinucleotide Phosphodiesterase Domain and a GGDEF Domain with ATPase Activity* , 2009, The Journal of Biological Chemistry.

[130]  E. Koonin,et al.  Predicted poxvirus FEN1-like nuclease required for homologous recombination, double-strand break repair and full-size genome formation , 2009, Proceedings of the National Academy of Sciences.

[131]  Sean R Eddy,et al.  A new generation of homology search tools based on probabilistic inference. , 2009, Genome informatics. International Conference on Genome Informatics.

[132]  C. Wolberger,et al.  Structure-based Mechanism of ADP-ribosylation by Sirtuins , 2009, The Journal of Biological Chemistry.

[133]  N. Moran,et al.  Convergent evolution of metabolic roles in bacterial co-symbionts of insects , 2009, Proceedings of the National Academy of Sciences.

[134]  L. Aravind,et al.  Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids , 2009, Cell cycle.

[135]  E. V. Nikolaev,et al.  Nicotinamide mononucleotide synthetase is the key enzyme for an alternative route of NAD biosynthesis in Francisella tularensis , 2009, Proceedings of the National Academy of Sciences.

[136]  E. Sonnhammer,et al.  Kalign2: high-performance multiple alignment of protein and nucleotide sequences allowing external features , 2008, Nucleic acids research.

[137]  L. Aravind,et al.  A new family of polymerases related to superfamily A DNA polymerases and T7-like DNA-dependent RNA polymerases , 2008, Biology Direct.

[138]  Liisa Holm,et al.  Searching protein structure databases with DaliLite v.3 , 2008, Bioinform..

[139]  A. Joachimiak,et al.  Structure of RapA, a Swi2/Snf2 protein that recycles RNA polymerase during transcription. , 2008, Structure.

[140]  L. Aravind,et al.  Analysis of DBC1 and its homologs suggests a potential mechanism for regulation of Sirtuin domain deacetylases by NAD metabolites , 2008, Cell cycle.

[141]  Christian Cole,et al.  The Jpred 3 secondary structure prediction server , 2008, Nucleic Acids Res..

[142]  K. Murakami,et al.  X-ray crystal structure of the polymerase domain of the bacteriophage N4 virion RNA polymerase , 2008, Proceedings of the National Academy of Sciences.

[143]  J. Berger,et al.  DNA topoisomerases: harnessing and constraining energy to govern chromosome topology , 2008, Quarterly Reviews of Biophysics.

[144]  Janusz M Bujnicki,et al.  Bacteriophage Mu Mom protein responsible for DNA modification is a new member of the acyltransferase superfamily , 2008, Cell cycle.

[145]  J. Abrahams,et al.  Crystal structure of the DNA repair enzyme ultraviolet damage endonuclease. , 2007, Structure.

[146]  D. Suck,et al.  Crystal structure of T4 endonuclease VII resolving a Holliday junction , 2007, Nature.

[147]  G. Fichant,et al.  A Key Presynaptic Role in Transformation for a Widespread Bacterial Protein: DprA Conveys Incoming ssDNA to RecA , 2007, Cell.

[148]  Jeff F. Miller,et al.  Diversity-generating retroelements. , 2007, Current opinion in microbiology.

[149]  H. Lindner Deubiquitination in virus infection , 2007, Virology.

[150]  R. Gerardy-Schahn,et al.  Characterization of a Novel Intramolecular Chaperone Domain Conserved in Endosialidases and Other Bacteriophage Tail Spike and Fiber Proteins* , 2007, Journal of Biological Chemistry.

[151]  L. Aravind,et al.  Comparative genomics and evolutionary trajectories of viral ATP dependent DNA-packaging systems. , 2007, Genome dynamics.

[152]  M. Lamers,et al.  Crystal Structure of the Catalytic α Subunit of E. coli Replicative DNA Polymerase III , 2006, Cell.

[153]  Karen N. Allen,et al.  Evolutionary genomics of the HAD superfamily: understanding the structural adaptations and catalytic diversity in a superfamily of phosphoesterases and allied enzymes. , 2006, Journal of molecular biology.

[154]  Erin M. Conlon,et al.  The forespore line of gene expression in Bacillus subtilis. , 2006, Journal of molecular biology.

[155]  Eugene V Koonin,et al.  Evolutionary genomics of nucleo-cytoplasmic large DNA viruses. , 2006, Virus research.

[156]  Brian C. Smith,et al.  Sir2 protein deacetylases: evidence for chemical intermediates and functions of a conserved histidine. , 2006, Biochemistry.

[157]  Robert Powers,et al.  Solution structure of Archaeglobus fulgidis peptidyl‐tRNA hydrolase (Pth2) provides evidence for an extensive conserved family of Pth2 enzymes in archea, bacteria, and eukaryotes , 2005, Protein science : a publication of the Protein Society.

[158]  R. Depping,et al.  The mono-ADP-ribosyltransferases Alt and ModB of bacteriophage T4: target proteins identified. , 2005, Biochemical and biophysical research communications.

[159]  Detlef D. Leipe,et al.  Origin and evolution of the archaeo-eukaryotic primase superfamily and related palm-domain proteins: structural insights and new members , 2005, Nucleic acids research.

[160]  Johannes Söding,et al.  The HHpred interactive server for protein homology detection and structure prediction , 2005, Nucleic Acids Res..

[161]  K. Kreuzer,et al.  Bacteriophage T4 Helicase Loader Protein gp59 Functions as Gatekeeper in Origin-dependent Replication in Vivo* , 2005, Journal of Biological Chemistry.

[162]  Mark Ptashne,et al.  Regulation of transcription: from lambda to eukaryotes. , 2005, Trends in biochemical sciences.

[163]  J. Roth,et al.  Regulation of NAD Synthesis by the Trifunctional NadR Protein of Salmonella enterica , 2005, Journal of bacteriology.

[164]  L. Aravind,et al.  The many faces of the helix-turn-helix domain: transcription regulation and beyond. , 2005, FEMS microbiology reviews.

[165]  E. Phizicky,et al.  A highly specific phosphatase that acts on ADP-ribose 1″-phosphate, a metabolite of tRNA splicing in Saccharomyces cerevisiae , 2005, Nucleic acids research.

[166]  M. Massiah,et al.  Structures and mechanisms of Nudix hydrolases. , 2005, Archives of biochemistry and biophysics.

[167]  Stewart Shuman,et al.  The polynucleotide ligase and RNA capping enzyme superfamily of covalent nucleotidyltransferases. , 2004, Current opinion in structural biology.

[168]  F. Blattner,et al.  Genome of Bacteriophage P1 , 2004, Journal of bacteriology.

[169]  Robert C. Edgar,et al.  MUSCLE: a multiple sequence alignment method with reduced time and space complexity , 2004, BMC Bioinformatics.

[170]  R. Hilgenfeld,et al.  Conformational Antagonism between Opposing Active Sites in a Bifunctional RelA/SpoT Homolog Modulates (p)ppGpp Metabolism during the Stringent Response , 2004, Cell.

[171]  H. Myllykallio,et al.  Two distinct pathways for thymidylate (dTMP) synthesis in (hyper)thermophilic Bacteria and Archaea. , 2004, Biochemical Society transactions.

[172]  Claudia Buchen,et al.  Structure of a bifunctional DNA primase-polymerase , 2004, Nature Structural &Molecular Biology.

[173]  M. Saier,et al.  Response regulators of bacterial signal transduction systems: Selective domain shuffling during evolution , 1995, Journal of Molecular Evolution.

[174]  Eugene V Koonin,et al.  Comparative genomics of the FtsK-HerA superfamily of pumping ATPases: implications for the origins of chromosome segregation, cell division and viral capsid packaging. , 2004, Nucleic acids research.

[175]  E. Phizicky,et al.  tRNAHis maturation: an essential yeast protein catalyzes addition of a guanine nucleotide to the 5' end of tRNAHis. , 2003, Genes & development.

[176]  Vivek Anantharaman,et al.  New connections in the prokaryotic toxin-antitoxin network: relationship with the eukaryotic nonsense-mediated RNA decay system , 2003, Genome Biology.

[177]  S. Brill,et al.  Slx1-Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1-Top3. , 2003, Genes & development.

[178]  E. Koonin,et al.  Evolutionary connection between the catalytic subunits of DNA-dependent RNA polymerases and eukaryotic RNA-dependent RNA polymerases and the origin of RNA polymerases , 2003, BMC Structural Biology.

[179]  Vivek Anantharaman,et al.  Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes , 2003, Genome Biology.

[180]  Raja Mazumder,et al.  Detection of novel members, structure–function analysis and evolutionary classification of the 2H phosphoesterase superfamily , 2002, Nucleic acids research.

[181]  Eugene V Koonin,et al.  Monophyly of class I aminoacyl tRNA synthetase, USPA, ETFP, photolyase, and PP‐ATPase nucleotide‐binding domains: implications for protein evolution in the RNA world , 2002, Proteins.

[182]  E. Koonin,et al.  Trends in protein evolution inferred from sequence and structure analysis. , 2002, Current opinion in structural biology.

[183]  E. Koonin,et al.  Classification and evolutionary history of the single-strand annealing proteins, RecT, Redβ, ERF and RAD52 , 2002, BMC Genomics.

[184]  E. Koonin,et al.  Common Origin of Four Diverse Families of Large Eukaryotic DNA Viruses , 2001, Journal of Virology.

[185]  E. Koonin,et al.  Prokaryotic homologs of the eukaryotic DNA-end-binding protein Ku, novel domains in the Ku protein and prediction of a prokaryotic double-strand break repair system. , 2001, Genome research.

[186]  Jie Liu,et al.  Mediator proteins orchestrate enzyme-ssDNA assembly during T4 recombination-dependent DNA replication and repair , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[187]  L. Amzel,et al.  The structure of ADP-ribose pyrophosphatase reveals the structural basis for the versatility of the Nudix family , 2001, Nature Structural Biology.

[188]  T. Sengupta,et al.  RegA proteins from phage T4 and RB69 have conserved helix-loop groove RNA binding motifs but different RNA binding specificities. , 2001, Nucleic acids research.

[189]  J. Champoux DNA topoisomerases: structure, function, and mechanism. , 2001, Annual review of biochemistry.

[190]  E V Koonin,et al.  SURVEY AND SUMMARY: holliday junction resolvases and related nucleases: identification of new families, phyletic distribution and evolutionary trajectories. , 2000, Nucleic acids research.

[191]  E. Koonin,et al.  Bacterial-type DNA holliday junction resolvases in eukaryotic viruses. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[192]  H. Masaki,et al.  A cytotoxic ribonuclease which specifically cleaves four isoaccepting arginine tRNAs at their anticodon loops. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[193]  N. Dulyaninova,et al.  Salvage pathway for NAD biosynthesis in Brevibacterium ammoniagenes: regulatory properties of triphosphate-dependent nicotinate phosphoribosyltransferase. , 2000, Biochimica et biophysica acta.

[194]  R. Lloyd,et al.  AP lyases and dRPases: commonality of mechanism. , 2000, Mutation research.

[195]  Detlef D. Leipe,et al.  The bacterial replicative helicase DnaB evolved from a RecA duplication. , 2000, Genome research.

[196]  E V Koonin,et al.  How many genes can make a cell: the minimal-gene-set concept. , 2000, Annual review of genomics and human genetics.

[197]  E. Koonin,et al.  DNA-binding proteins and evolution of transcription regulation in the archaea. , 1999, Nucleic acids research.

[198]  Michael Y. Galperin,et al.  A specialized version of the HD hydrolase domain implicated in signal transduction. , 1999, Journal of molecular microbiology and biotechnology.

[199]  A. Zinn,et al.  New gene family defined by MORC, a nuclear protein required for mouse spermatogenesis. , 1999, Human molecular genetics.

[200]  D. Turner,et al.  Transient ADP-ribosylation of a 2′-Phosphate Implicated in Its Removal from Ligated tRNA during Splicing in Yeast* , 1999, The Journal of Biological Chemistry.

[201]  E V Koonin,et al.  The HD domain defines a new superfamily of metal-dependent phosphohydrolases. , 1998, Trends in biochemical sciences.

[202]  Detlef D. Leipe,et al.  Toprim--a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins. , 1998, Nucleic acids research.

[203]  E V Koonin,et al.  Phosphoesterase domains associated with DNA polymerases of diverse origins. , 1998, Nucleic acids research.

[204]  E. Marusich,et al.  Chaperones in bacteriophage T4 assembly. , 1998, Biochemistry. Biokhimiia.

[205]  H. Dressman,et al.  The roles of the bacteriophage T4 r genes in lysis inhibition and fine-structure genetics: a new perspective. , 1998, Genetics.

[206]  T A Jones,et al.  Structure of Escherichia coli ribokinase in complex with ribose and dinucleotide determined to 1.8 A resolution: insights into a new family of kinase structures. , 1998, Structure.

[207]  P. Bork,et al.  Merging extracellular domains: fold prediction for laminin G-like and amino-terminal thrombospondin-like modules based on homology to pentraxins. , 1998, Journal of molecular biology.

[208]  R. Müller,et al.  Overexpression and Structural Characterization of the Phage T4 Protein DsbA , 1998, Biological chemistry.

[209]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[210]  E. Koonin,et al.  A minimal gene set for cellular life derived by comparison of complete bacterial genomes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[211]  David A. Matthews,et al.  Structure of the Human Cytomegalovirus Protease Catalytic Domain Reveals a Novel Serine Protease Fold and Catalytic Triad , 1996, Cell.

[212]  S. Shuman,et al.  RNA capping enzyme and DNA ligase: a superfamily of covalent nucleotidyl transferases , 1995, Molecular microbiology.

[213]  R. Hendrix,et al.  Genetic basis of bacteriophage HK97 prohead assembly. , 1995, Journal of molecular biology.

[214]  L. Snyder Phage‐exclusion enzymes: a bonanza of biochemical and cell biology reagents? , 1995, Molecular microbiology.

[215]  H. Ackermann,et al.  Bacteriophages from Bombyx mori. , 1994, Archives of virology.

[216]  E. Nudler,et al.  Bacteriophage T4 Alc protein: A transcription termination factor sensing local modification of DNA , 1993, Cell.

[217]  Peter J. Rousseeuw,et al.  Finding Groups in Data: An Introduction to Cluster Analysis , 1990 .

[218]  P Argos,et al.  An attempt to unify the structure of polymerases. , 1990, Protein engineering.

[219]  K. Shanmugam,et al.  Identification of a new gene, molR, essential for utilization of molybdate by Escherichia coli , 1990, Journal of bacteriology.

[220]  G. Michaud,et al.  Membrane-associated assembly of a phage T4 DNA entrance vertex structure studied with expression vectors. , 1989, Journal of molecular biology.

[221]  V. Stanisich,et al.  Location and characterization of two functions on RP1 that inhibit the fertility of the IncW plasmid R388. , 1989, Journal of general microbiology.

[222]  G. Wilson,et al.  Genetic analysis of bacteriophage T4 transducing bacteriophages , 1982, Journal of virology.

[223]  P. López,et al.  Influence of Bacteriophage PBS1 and φW-14 Deoxyribonucleic Acids on Homologous Deoxyribonucleic Acid Uptake and Transformation in Competent Bacillus subtilis , 1980 .

[224]  A. Johnson,et al.  Mechanism of action of the cro protein of bacteriophage lambda. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[225]  W. Anderson,et al.  Purification and properties of bacteriophage T4-induced RNA ligase. , 1976, Archives of biochemistry and biophysics.

[226]  D. McCorquodale,et al.  Transfection of Escherichia coli spheroplasts. VI. Transfection of nonpermissive spheroplasts by T5 and BF23 bacteriophage DNA carrying amber mutations in DNA transfer genes , 1975, Journal of virology.

[227]  O. Uhlenbeck,et al.  T4-induced RNA ligase joins single-stranded oligoribonucleotides. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[228]  G. Donelli,et al.  Structure and physico-chemical properties of bacteriophage G. I. Arrangement of protein subunits and contraction process of tail sheath. , 1972, Journal of molecular biology.

[229]  G. N. Lance,et al.  Computer Programs for Hierarchical Polythetic Classification ("Similarity Analyses") , 1966, Comput. J..

[230]  R. Feynman,et al.  Mapping experiments with r mutants of bacteriophage T4D. , 1962, Genetics.